Arsenic trioxide induces multiple myeloma cell apoptosis viadisruption of mitochondrial transmembrane potentials and activation of caspase-3
10.3760/j.issn:0366-6999.2001.01.004
- VernacularTitle:氧化砷通过线粒体跨膜电位下降与激活Caspase-3诱导多发性骨髓瘤细胞凋亡
- Author:
Peimin JIA
1
;
Guoqiang CHEN
;
Xiaojun HUANG
;
Xun CAI
;
Jie YANG
;
Long WANG
;
Yuhong ZHOU
;
Yulei SHEN
;
Li ZHOU
;
Yun YU
;
Saijuan CHEN
;
Xueguang ZHANG
;
Zhenyi WANG
Author Information
1. 上海第二医科大学附属瑞金医院
- Keywords:
arsenic trioxide;
multiple myeloma;
apoptosis;
mitochondrial transmembrane potentials
- From:
Chinese Medical Journal
2001;114(1):19-24
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. Methods Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (△Ψm) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. Results Zero point one to 0.5?μmol/L As2O3 inhibited cell proliferation and 2.0?μmol/L As2O3 induced cell apoptosis, while 1.0?μmol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (△Ψm) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced △Ψm collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. Conclusion As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.
